不同肠型孤独症患儿的肠道菌群和发育特征OACSTPCD
Characteristics of gut microbiota and development in children with different enterotypes of autism
目的:并发胃肠道症状的孤独症谱系障碍(autism spectrum disorder,ASD)患儿常伴随肠道菌群异常,肠道菌群及其代谢物可能通过迷走神经、免疫、代谢途径参与ASD发病.本研究旨在探讨不同肠型ASD患儿的肠道菌群特征、发育特征和胃肠道症状,进一步探讨肠道菌群和生长、发育的联系.方法:选取2023年1月至2023年6月在上海市第六人民医院进行康复训练的13例ASD患儿.采用宏基因组学检测患儿粪便样本的肠道菌群,并进行肠型分析.采用香农指数和辛普森指数衡量微生物群落的均匀性和多样性,主坐标分析法进行β多样性分析.采用Kraken2对样品的有效序列进行注释分类,研究样品物种组成.采用线性判别分析找到组间在丰度上有显著差异的物种.采用格里菲斯发育评估量表中文版(Griffiths Development Scales-Chinese Edition,GDS-C)评估患儿的生长、发育,同时评估ASD患儿的胃肠道症状.结果:13例ASD患儿中,8例为普雷沃氏菌型(普雷沃氏菌组),4例为拟杆菌型(拟杆菌组),1例为混合肠型(混合肠型组).普雷沃氏菌组的香农指数和辛普森指数均高于拟杆菌组,表明普雷沃氏菌组的丰度和均匀度较高.主坐标分析图结果显示2组的聚集范围差异具有统计学意义(P=0.013),β多样性有明显区别.2组在门、属、种水平的主要细菌组成和丰度的差异有统计学意义.普雷沃氏菌组差异较大的物种有真杆菌目(Eubacteriales)、梭菌纲(Clostridia)、厌氧棒菌属(Anaerotignum)和链形杆菌属(Catenibacterium).拟杆菌组的差异较大的物种有居海事城球杆菌属(Phocaeicola)、拟杆菌目(Bacteroidales)、拟杆菌纲(Bacteroidia)、拟杆菌科(Bacteroidaceae)和拟杆菌门(Bacteroidota).GDS-C评估结果显示:2组随访前、随访后GDS-C得分在5个领域上的组间比较差异均无统计学意义(均P>0.05),普雷沃氏菌组组内比较在手眼协调和表现方面的有明显改善,而拟杆菌组组内比较在运动方面有明显改善,且2组的差异物种分别与GDS-C得分存在相关性.普雷沃氏菌型并发便秘的ASD患儿较无便秘的患儿有更多的拟杆菌属和脱硫弧菌.结论:普雷沃氏菌型和拟杆菌型的ASD患儿的生长、发育情况显著不同,并且肠道菌群和生长、发育具有相关性.
Objective:Children with autism spectrum disorder(ASD)who exhibit concurrent gastrointestinal symptoms often have abnormal intestinal microbiota.The microbiota and their metabolites may participate in the pathogenesis of ASD through vagus nerve,immune,and metabolic pathways.This study aims to explore the characteristics of the intestinal microbiota,developmental characteristics,and gastrointestinal symptoms in children with ASD of different intestinal types,and further explore the relationship between the intestinal microbiota and growth and development. Methods:A total of 13 children with ASD undergoing rehabilitation training at Shanghai Sixth People's Hospital from January 2023 to June 2023 were selected for the study.Metagenomics was used to detect the intestinal microbiota of fecal samples from these children,and intestinal types were classified.Homogeneity and diversity of microbial communities were measured by Shannon index and Simpson index,and β-diversity was analyzed by principal coordinates analysis method.Effective sequences of the samples were annotated and classified using Kraken2 to study the species composition.Species with significant differences in abundance between groups were identified by linear discriminant analysis.The Griffiths Development Scales-Chinese Edition(GDS-C)was used to evaluate the growth and development of the children,and their gastrointestinal symptoms were also assessed. Results:Of the 13 children with ASD,8 belonged to a Prevotella group,4 to a Bacteroides group,and 1 to a mixed intestinal type group.Shannon index and Simpson index in the Prevotella group were higher than in the Bacteroides group,indicating higher abundance and evenness.The results of principal coordinates analysis showed statistically significant differences in the clustering range between the 2 groups(P=0.013),with significant differences in β-diversity.There were statistically significant differences in the main bacterial compositions and abundance at the phylum,genus,and species levels between the 2 groups.Species with significant differences in the Prevotella group included Eubacteriales,Clostridia,Anaerotignum,and Catenibacterium.In the Bacteroides group,species with significant differences included Phocaeicola,Bacteroidales,Bacteroidia,Bacteroidaceae,and Bacteroidota.GDS-C evaluation results showed no statistically significant differences in scores between the 2 groups before and after follow-up in the domains of locomotor,personal-social,language,hand-eye coordination,and performance.The intra-group comparison of the Prevotella group showed significant improvement in hand-eye coordination and performance(all P>0.05),while the intra-group comparison of the Bacteroides group showed significant improvement in locomotor activities.The different species between the 2 groups were correlated with the GDS-C scores.Children with ASD and constipation in the Prevotella group had more species from the genus Bacteroides and desulphurvibrio than those children without constipation. Conclusion:The growth and development of gut microbiota in children with ASD of Prevotella and Bacteroides types are significantly different,and there is a correlation between the gut microbiota and growth and development.
韦金盈;刘田雨;张凤;陈嘉怡;陈娟娟;袁延涵;张金萍
上海海洋大学食品学院,上海 201306上海市第六人民医院儿科,上海 201306
孤独症谱系障碍胃肠微生物组宏基因组学格里菲斯发育评估
autism spectrum disordergastrointestinal microbiomemetagenomicsGriffiths developmental assessment
《临床与病理杂志》 2024 (002)
230-241 / 12
上海市第六人民医院横向科研项目(XCT0273003).This work was supported by the Safety and Efficacy of Fecal Microbiota Transplantation in Children with Autism Spectrum Disorder,China(XCT0273003).
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